AHA/ASA guideline recommendations for of Early management of acute ischemic stroke

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]

2015 AHA/ASA Guidelines for the early Management of Acute Ischemic Stroke

Prehospital Stroke Management

Class I

"1. To increase both the number of patients who are treated and the quality of care, educational stroke programs for physicians, hospital personnel, and EMS personnel are recommended. (Level of Evidence: B)"

"2. Activation of the 9-1-1 system by patients or other members of the public is strongly recommended. Dispatchers should make stroke a priority dispatch, and transport times should be minimized. (Level of Evidence: B)"

"3. Prehospital care providers should use prehospital stroke assessment tools, such as the Los Angeles, Prehospital Stroke Screen or Cincinnati Prehospital Stroke Scale . (Level of Evidence: B)"

"4. EMS personnel should begin the initial management of stroke in the field. Development of a stroke protocol to be used by EMS personnel is strongly encouraged. (Level of Evidence: B)"

"5. Patients should be transported rapidly to the closest available certified PSC or CSC or, if no such centers exist, the most appropriate institution that provides emergency stroke care as described in the statement. (Level of Evidence: A)"

"6. EMS personnel should provide prehospital notification to the receiving hospital that a potential stroke patient is en route so that the appropriate hospital resources may be mobilized before patient arrival. (Level of Evidence: B)"

Designation of Stroke Centers and Stroke Care, Quality Improvement Process

Class I

"1. The creation of PSCs is recommended. The organization of such resources will depend on local resources. The stroke system design of regional ASRHs and PSCs that provide emergency care and that are closely associated with a CSC, which provides more extensive care, has considerable appeal. (Level of Evidence: B)"

"2. Certification of stroke centers by an independent external body, such as TJC or state health department, is recommended. Additional medical centers should seek such certification. (Level of Evidence: B)"

"3. Healthcare institutions should organize a multidisciplinary quality improvement committee to review and monitor stroke care quality benchmarks, indicators, evidence-based practices, and outcomes. The formation of a clinical process improvement team and the establishment of a stroke care data bank are helpful for such quality of care assurances. The data repository can be used to identify the gaps or disparities in quality stroke care. Once the gaps have been identified, specific interventions can be initiated to address these gaps or disparities. (Level of Evidence: B)"

"4. For patients with suspected stroke, EMS should bypass hospitals that do not have resources to treat stroke and go to the closest facility most capable of treating acute stroke. (Level of Evidence: B)"

"5. For sites without in-house imaging interpretation expertise, teleradiology systems approved by the Food and Drug Administration (FDA) or equivalent organization are recommended for timely review of brain CT and MRI scans in patients with suspected acute stroke. (Level of Evidence: B)"

"6. When implemented within a telestroke network, teleradiology systems approved by the FDA (or equivalent organization) are useful in supporting rapid imaging interpretation in time for fibrinolysis decision making. (Level of Evidence: B)"

"7. The development of CSCs is recommended. (Level of Evidence: C)"

Class IIa

"1. Implementation of telestroke consultation in conjunction with stroke education and training for healthcare providers can be useful in increasing the use of intravenous rtPA at community hospitals without access to adequate onsite stroke expertise (Level of Evidence: B)"

"2. The creation of ASRHs can be useful. As with PSCs, the organization of such resources will depend on local resources. The stroke system design of regional ASRHs and PSCs that provide emergency care and that are closely associated with a CSC, which provides more extensive care, has considerable appeal (Level of Evidence: C)"

Emergency Triage and Initial Evaluation

Class I

"1. An organized protocol for the emergency evaluation of patients with suspected stroke is recommended. The goal is to complete an evaluation and to begin fibrinolytic treatment within 60 minutes of the patient’s arrival in an ED. Designation of an acute stroke team that includes physicians, nurses, and laboratory/radiology personnel is encouraged. Patients with stroke should have a careful clinical assessment, including neurological examination. (Level of Evidence: B)"

"2. The use of a stroke rating scale, preferably the NIHSS, is recommended. (Level of Evidence: B)"

"3. A limited number of hematologic, coagulation, and biochemistry tests are recommended during the initial emergency evaluation, and only the assessment of blood glucose must precede the initiation of intravenous rtPA. (Level of Evidence: B)"

"4. Baseline electrocardiogram assessment is recommended in patients presenting with acute ischemic stroke but should not delay initiation of intravenous rtPA. (Level of Evidence: B)"

"5. Baseline troponin assessment is recommended in patients presenting with acute ischemic stroke but should not delay initiation of intravenous rtPA. (Level of Evidence: C)"

Class IIb

"1. The usefulness of chest radiographs in the hyperacute stroke setting in the absence of evidence of acute pulmonary, cardiac, or pulmonary vascular disease is unclear. If obtained, they should not unnecessarily delay administration of fibrinolysis. (Level of Evidence: B)"

Parenchymal Brain Imaging

Recommendations for Patients With Acute Cerebral Ischemic Symptoms That Have Not Yet Resolved

Class I

"1. Emergency imaging of the brain is recommended before initiating any specific therapy to treat acute ischemic stroke. In most instances, NECT will provide the necessary information to make decisions about emergency management. (Level of Evidence: A)"

"2. Either NECT or MRI is recommended before intravenous rtPA administration to exclude ICH (absolute contraindication) and to determine whether CT hypodensity or MRI hyperintensity of ischemia is present. (Level of Evidence: A)"

"3. Intravenous fibrinolytic therapy is recommended in the setting of early ischemic changes (other than frank hypodensity) on CT, regardless of their extent.(Level of Evidence: A)"

"4. A noninvasive intracranial vascular study is strongly recommended during the initial imaging evaluation of the acute stroke patient if either intra-arterial fibrinolysis or mechanical thrombectomy is contemplated for management but should not delay intravenous rtPA if indicated (Level of Evidence: B)"

"5. In intravenous fibrinolysis candidates, the brain imaging study should be interpreted within 45 minutes of patient arrival in the ED by a physician with expertise in reading CT and MRI studies of the brain parenchyma (Class I; Level of Evidence C) . (Level of Evidence: C)"

Class IIb

"1. CT perfusion and MRI perfusion and diffusion imaging, including measures of infarct core and penumbra, may be considered for the selection of patients for acute reperfusion therapy beyond the time windows for intravenous fibrinolysis. These techniques provide additional information that may improve diagnosis, mechanism, and severity of ischemic stroke and allow more informed clinical decision making. (Level of Evidence: B)"

Class III

"1. Frank hypodensity on NECT may increase the risk of hemorrhage with fibrinolysis and should be considered in treatment decisions. If frank hypodensity involves more than one third of the MCA territory, intravenous rtPA treatment should be withheld. (Level of Evidence: A)"

Recommendations for Patients With Cerebral Ischemic Symptoms That Have Resolved

Class I

"1. Noninvasive imaging of the cervical vessels should be performed routinely as part of the evaluation of patients with suspected TIAs. (Level of Evidence: A)"

"2. Noninvasive imaging by means of CTA or MRA of the intracranial vasculature is recommended to exclude the presence of proximal intracranial stenosis and/or occlusion and should be obtained when knowledge of intracranial stenoocclusive disease will alter management. Reliable diagnosis of the presence and degree of intracranial stenosis requires the performance of catheter angiography to confirm abnormalities detected with noninvasive testing.(Level of Evidence: A)"

"3. Patients with transient ischemic neurological symptoms should undergo neuroimaging evaluation within 24 hours of symptom onset or as soon as possible in patients with delayed presentations. MRI, including DWI, is the preferred brain diagnostic imaging modality. If MRI is not available, head CT should be performed. (Level of Evidence: B)"

General Supportive Care and Treatment of Acute Complications

Class I

"1. Cardiac monitoring is recommended to screen for atrial fibrillation and other potentially serious cardiac arrhythmias that would necessitate emergency cardiac interventions. Cardiac monitoring should be performed for at least the first 24 hours. (Level of Evidence: B)"

"2. Patients who have elevated blood pressure and are otherwise eligible for treatment with intravenous rtPA should have their blood pressure carefully lowered so that their systolic blood pressure is <185 mm Hg and their diastolic blood pressure is <110 mm Hg before fibrinolytic therapy is initiated. If medications are given to lower blood pressure, the clinician should be sure that the blood pressure is stabilized at the lower level before beginning treatment with intravenous rtPA and maintained below 180/105 mm Hg for at least the first 24 hours after intravenous rtPA treatment. (Level of Evidence: B)"

"3. Airway support and ventilatory assistance are recommended for the treatment of patients with acute stroke who have decreased consciousness or who have bulbar dysfunction that causes compromise of the airway. (Level of Evidence: C)"

"4. Supplemental oxygen should be provided to maintain oxygen saturation >94%. (Level of Evidence: C)"

"5. Sources of hyperthermia (temperature >38°C) should be identified and treated, and antipyretic medications should be administered to lower temperature in hyperthermic patients with stroke. (Level of Evidence: C)"

"6. Until other data become available, consensus exists that the previously described blood pressure recommendations should be followed in patients undergoing other acute interventions to recanalize occluded vessels, including intra-arterial fibrinolysis Patients with transient ischemic neurological symptoms should undergo neuroimaging evaluation within 24 hours of symptom onset or as soon as possible in patients with delayed presentations. MRI, including DWI, is the preferred brain diagnostic imaging modality. If MRI is not available, head CT should be performed. (Level of Evidence: C )"

"7. In patients with markedly elevated blood pressure who do not receive fibrinolysis, a reasonable goal is to lower blood pressure by 15% during the first 24 hours after onset of stroke. The level of blood pressure that would mandate such treatment is not known, but consensus exists that medications should be withheld unless the systolic blood pressure is >220 mm Hg or the diastolic blood pressure is >120 mm Hg. (Level of Evidence: C)"

"8. Hypovolemia should be corrected with intravenous normal saline, and cardiac arrhythmias that might be reducing cardiac output should be corrected. (Level of Evidence: C)"

"9. Hypoglycemia (blood glucose <60 mg/dL) should be treated in patients with acute ischemic stroke. (Level of Evidence: C)"

Class IIa

"1. Evidence from one clinical trial indicates that initiation of antihypertensive therapy within 24 hours of stroke is relatively safe. Restarting antihypertensive medications is reasonable after the first 24 hours for patients who have preexisting hypertension and are neurologically stable unless a specific contraindication to restarting treatment is known. (Level of Evidence: B)"

"2. No data are available to guide selection of medications for the lowering of blood pressure in the setting of acute ischemic stroke.(Level of Evidence: C)"

"3. Evidence indicates that persistent in-hospital hyperglycemia during the first 24 hours after stroke is associated with worse outcomes than normoglycemia, and thus, it is reasonable to treat hyperglycemia to achieve blood glucose levels in a range of 140 to 180 mg/dL and to closely monitor to prevent hypoglycemia in patients with acute ischemic stroke. (Level of Evidence: C)"

Class IIa

"1. The management of arterial hypertension in patients not undergoing reperfusion strategies remains challenging. Data to guide recommendations for treatment are inconclusive or conflicting. Many patients have spontaneous declines in blood pressure during the first 24 hours after onset of stroke. Until more definitive data are available, the benefit of treating arterial hypertension in the setting of acute ischemic stroke is not well established. Patients who have malignant hypertension or other medical indications for aggressive treatment of blood pressure should be treated accordingly. (Level of Evidence: C)"

Class III

"1. Supplemental oxygen is not recommended in nonhypoxic patients with acute ischemic stroke. (Level of Evidence: B)"

Intravenous Fibrinolysis

Class I

"1. Intravenous rtPA (0.9 mg/kg, maximum dose 90mg) is recommended for selected patients who may be treated within 3 hours of onset of ischemic stroke. (Level of Evidence: A)"

"2. In patients eligible for intravenous rtPA, benefit of therapy is time dependent, and treatment should be initiated as quickly as possible. The door-to-needle time (time of bolus administration) should be within 60 minutes from hospital arrival . (Level of Evidence: A)"

"3. Intravenous rtPA (0.9 mg/kg, maximum dose 90mg) is recommended for administration to eligible patients who can be treated in the time period of 3 to 4.5 hours after stroke onset. The eligibility criteria for treatment in this time period are similar to those for people treated at earlier time periods within 3 hours, with the following additional exclusion criteria: patients >80 years old, those taking oral anticoagulants regardless of INR, those with a baseline NIHSS score >25, those with imaging evidence of ischemic injury involving more than one third of the MCA territory, or those with a history of both stroke and diabetes mellitus. . (Level of Evidence: B)"

"4. Intravenous rtPA is reasonable in patients whose blood pressure can be lowered safely (to below 185/110 mm Hg) with antihypertensive agents, withthe physician assessing the stability of the blood pressure before starting intravenous rtPA .(Level of Evidence: B)"

"5. In patients undergoing fibrinolytic therapy, physicians should be aware of and prepared to emergently treat potential side effects, including bleeding complications and angioedema that may cause partial airway obstruction. (Level of Evidence: B)"

Class IIa

"1. Intravenous rtPA is reasonable in patients with a seizure at the time of onset of stroke if evidence suggests that residual impairments are secondary to stroke and not a postictal phenomenon. (Level of Evidence: C)"

Class IIb

"1. The effectiveness of sonothrombolysis for treatment of patients with acute stroke is not well established. (Level of Evidence: B)"

"2. The usefulness of intravenous administration of tenecteplase, reteplase, desmoteplase, urokinase, or other fibrinolytic agents and the intravenous administration of ancrod or other defibrinogenating agents is not well established, and they should only be used in the setting of a clinical trial. (Level of Evidence: B)"

"3. The effectiveness of intravenous treatment with rtPA is not well established and requires further study for patients who can be treated in the time period of 3 to 4.5 hours after stroke but have 1 or more of the following exclusion criteria: (1) patients >80 years old, (2) those taking oral anticoagulants, even with INR ≤1.7, (3) those with a baseline NIHSS score >25, or (4) those with a history of both stroke and diabetes mellitus. (Level of Evidence: C)"

"4. Use of intravenous fibrinolysis in patients with conditions of mild stroke deficits, rapidly improving stroke symptoms, major surgery in the preceding 3 months, and recent myocardial infarction may be considered, and potential increased risk should be weighed against the anticipated benefits. (Level of Evidence: C)"

Class III (Harm)

"1. The intravenous administration of streptokinase for treatment of stroke is not recommended. (Level of Evidence: A)"

"2. The use of intravenous rtPA in patients taking direct thrombin inhibitors or direct factor Xa inhibitors may be harmful and is not recommended unless sensitive laboratory tests such as aPTT, INR, platelet count, and ECT, TT, or appropriate direct factor Xa activity assays are normal, or the patient has not received a dose of these agents for >2 days (assuming normal renal metabolizing function). Similar consideration should be given to patients being considered for intra-arterial rtPA. (Level of Evidence: C)"

Endovascular Interventions

Class I

"1. Patients eligible for intravenous rtPA should receive intravenous rtPA even if intra-arterial treatments are being considered. (Level of Evidence: A)"

"2. Intra-arterial fibrinolysis is beneficial for treatment of carefully selected patients with major ischemic strokes of <6 hours’ duration caused by occlusions of the MCA who are not otherwise candidates for intravenous rtPA. The optimal dose of intra-arterial rtPA is not well established, and rtPA does not have FDA approval for intra-arterial use. (Level of Evidence: B)"

"3. As with intravenous fibrinolytic therapy, reduced time from symptom onset to reperfusion with intraarterial therapies is highly correlated with better clinical outcomes, and all efforts must be undertaken to minimize delays to definitive therapy. (Level of Evidence: B)"

"4. Intra-arterial treatment requires the patient to be at an experienced stroke center with rapid access to cerebral angiography and qualified interventionalists. An emphasis on expeditious assessment and treatment should be made. Facilities are encouraged to define criteria that can be used to credential individuals who can perform intra-arterial revascularization procedures. Outcomes on all patients should be tracked. (Level of Evidence: C)"

"5. When mechanical thrombectomy is pursued, stent retrievers such as Solitaire FR and Trevo are generally preferred to coil retrievers such as Merci. The relative effectiveness of the Penumbra System versus stent retrievers is not yet characterized. ( (Level of Evidence: A)"

Class IIa

"1. The Merci, Penumbra System, Solitaire FR, and Trevo thrombectomy devices can be useful in achieving recanalization alone or in combination with pharmacological fibrinolysis in carefully selected patients. Their ability to improve patient outcomes has not yet been established. These devices should continue to be studied in randomized controlled trials to determine the efficacy of such treatments in improving patient outcomes. (Level of Evidence: B)"

"2. Intra-arterial fibrinolysis or mechanical thrombectomy is reasonable in patients who have contraindications to the use of intravenous fibrinolysis. (Level of Evidence: C)"

Class IIb

"1. Rescue intra-arterial fibrinolysis or mechanical thrombectomy may be reasonable approaches to recanalization in patients with large-artery occlusion who have not responded to intravenous fibrinolysis. Additional randomized trial data are needed. (Level of Evidence: B)"

"2. The usefulness of mechanical thrombectomy devices other than the Merci retriever, the Penumbra System, Solitaire FR, and Trevo is not well established. (Level of Evidence: C )"

"3. The usefulness of emergent intracranial angioplasty and/or stenting is not well established. These procedures should be used in the setting of clinical trials. (Level of Evidence: C)"

"4. The usefulness of emergent angioplasty and/or stenting of the extracranial carotid or vertebral arteries in unselected patients is not well established. Use of these techniques may be considered in certain circumstances, such as in the treatment of acute ischemic stroke resulting from cervical atherosclerosis or dissection. Additional randomized trial data are needed (Level of Evidence: C)"

Anticoagulants

Class IIb

"1. At present, the usefulness of argatroban or other thrombin inhibitors for treatment of patients with acute ischemic stroke is not well established. These agents should be used in the setting of clinical trials. (Level of Evidence: B)"

"2. The usefulness of urgent anticoagulation in patients with severe stenosis of an internal carotid artery ipsilateral to an ischemic stroke is not well established. (Level of Evidence: B)"

Class III (Harm)

"1. Urgent anticoagulation, with the goal of preventing early recurrent stroke, halting neurological worsening, or improving outcomes after acute ischemic stroke, is not recommended for treatment of patients with acute ischemic stroke. (Level of Evidence: C)"

"2. Urgent anticoagulation for the management of noncerebrovascular conditions is not recommended for patients with moderate-to-severe strokes because of an increased risk of serious intracranial hemorrhagic complications. (Level of Evidence: A)"

"3. Initiation of anticoagulant therapy within 24 hours of treatment with intravenous rtPA is not recommended. (Level of Evidence: B)"

Antiplatelets

Class I

"1. Oral administration of aspirin (initial dose is 325 mg) within 24 to 48 hours after stroke onset is recommended for treatment of most patients. (Level of Evidence: A)"

Class IIb

"1. The usefulness of clopidogrel for the treatment of acute ischemic stroke is not well established. Further research testing the usefulness of the emergency administration of clopidogrel in the treatment of patients with acute stroke is required (Level of Evidence: C)"

"2. The efficacy of intravenous tirofiban and eptifibatide is not well established, and these agents should be used only in the setting of clinical trials. (Level of Evidence: C)"

Class III (Harm)

"1. Aspirin is not recommended as a substitute for other acute interventions for treatment of stroke, including intravenous rtPA. (Level of Evidence: B)"

"2. The administration of other intravenous antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor is not recommended. Further research testing the usefulness of emergency administration of these medications as a treatment option in patients with acute ischemic stroke is required. (Level of Evidence: B)"

"3. The administration of aspirin (or other antiplatelet agents) as an adjunctive therapy within 24 hours of intravenous fibrinolysis is not recommended. (Level of Evidence: C)"

Volume Expansion, Vasodilators, and Induced Hypertension

Class I

"1. In exceptional cases with systemic hypotension producing neurological sequelae, a physician may prescribe vasopressors to improve cerebral blood flow. If drug-induced hypertension is used, close neurological and cardiac monitoring is recommended. (Level of Evidence: C)"

Class IIb

"1. The administration of high-dose albumin is not well established as a treatment for most patients with acute ischemic stroke until further definitive evidence regarding efficacy becomes available. (Level of Evidence: B)"

"2. At present, use of devices to augment cerebral blood flow for the treatment of patients with acute ischemic stroke is not well established. These devices should be used in the setting of clinical trials. (Level of Evidence: B)"

"3. The usefulness of drug-induced hypertension in patients with acute ischemic stroke is not well established. Induced hypertension should be performed in the setting of clinical trials . (Level of Evidence: B)"

Class III (Harm)

"1. Hemodilution by volume expansion is not recommended for treatment of patients with acute ischemic stroke (Level of Evidence: A)"

"2. The administration of vasodilatory agents, such as pentoxifylline, is not recommended for treatment of patients with acute ischemic stroke. (Level of Evidence: A)"

Neuroprotective Agents

Class IIa

"1. Among patients already taking statins at the time of onset of ischemic stroke, continuation of statin therapy during the acute period is reasonable. (Level of Evidence: B)"